HHV-6 & 7 found in spinal fluid of immunocompetent children suspected of CNS infection

An Italian study on immunocompetent children with suspected CNS infections found HHV-6 and HHV-7 DNA in 4.2% and 4.8% of 304 cerebrospinal fluid (CSF) samples, respectively. Although once considered rare in the immunocompetent, recent studies with more sensitive methods have found HHV-6 in the CSF of 4-17% of immunocompetent children with seizures or suspected CNS infections.

The Japanese seem to have the highest rate of HHV-6 DNA found in these cases. A 2011 survey of 983 encephalopathy/encephalitis cases in Japan found HHV-6 DNA in 17% of cases and a viral cause in 60% of immunocompetent children. Influenza virus was the most common virus found at 27%, followed by HHV-6 at 17% and rotavirus at 4% (Hoshino 2011).

Another Japanese study of 105 CSF specimens from children with encephalopathy/encephalitis found 9.5% to be positive for HHV-6 and 1.9% for HHV-7 (Wada 2009).

In an Iranian study of 114 children under 2 years of age, 8.8% presenting with possible encephalitis tested positive for HHV-6 by PCR (Yavarian 2014).

An Austrian group also tested 2417 CSF samples from patients with neurological disorders to determine the prevalence of several viruses, but the threshold was set so high (1000 copies/ml) that HHV-6 was detected in only 4 patients, or 0.17% of the population, which is less than the 1% of cases expected for chromosomal integration (Kleines 2014). Among 239 children admitted for encephalitis before the age of 6 months at the Children’s Hospital of Colorado, 5 (2.1%) tested positive for HHV-6 (Messacar 2015). However, fewer than 10% of children in the US acquire HHV-6 by 6 months (Zerr 2005), so this was not the optimum time period to test for HHV-6.

HHV-6 and HHV-7 are significant causes of neurological morbidity and are present in the blood of 17% of children hospitalized for suspected encephalitis in the UK (Ward 2005). Approximately 1/3 of status epilepticus cases are triggered by HHV-6B (Epstein 2012), as measured by qPCR in serum and mRNA studies.

The Italian group found enterovirus to be the most common pathogen found at 15.2%, and among newborns, the incidence rose to 70%. Eleven viruses were studied, and overall, a virus was identified in 21% of samples.

The study authors note that the International Encephalitis Consortium does not recommend that HHV-6 & 7 be included in the initial workup; only enterovirus, herpes simplex, and human parechoviruses are currently recommended. Herpes simplex (HSV1) was found in only 1% of those tested in the Italian study and less than 1% in the Japanese national survey of encephalopathy/encephalitis.

For more information on the Italian study read the full paper ( Parisi 2016).

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The HHV-6 Foundation in a non-profit entity founded to encourage scientific exchange between investigators and to provide pilot grants for promising scientific and clinical research on the under- appreciated viruses HHV-6A and HHV-6B.

The Foundation sponsors international conferences and supports scientists and clinicians seeking to clarify the role of the two HHV-6 viruses in disease. Since HHV-6A and HHV-6B can smolder in the brain and other organs without circulating in the peripheral blood or plasma, identifying chronic infection is a challenge.